title: Cutting edge: Direct recognition of infected cells by CD4 T cells is required for control of intracellular Mycobacterium tuberculosis in vivo.
abstract: Effector T cells control intracellular infection by secreting cytokines and through contact-dependent cytolysis. Because cytokines can diffuse and act at a distance, we determined whether cytokine diffusion is sufficient to control Mycobacterium tuberculosis or whether direct recognition of infected cells by CD4 T cells is required. Using MHC class II (MHC II) mixed bone marrow chimeras, we compared the bacterial burdens in lung myeloid cells that were capable (MHC II(+/+)) or not (MHC II(-/-)) of being recognized by CD4 T cells. MHC II(+/+) cells had lower bacterial burdens than did MHC II(-/-) cells. CD4 T cell depletion increased the number of bacteria associated with MHC II(+/+)cells but not MHC II(-/-) cells, indicating that direct recognition of infected cells by CD4 T cells is required for control of intracellular M. tuberculosis. These results show that the effector mechanisms required for CD4 T cell control of distinct intracellular pathogens differ and that long-range cytokine diffusion does not contribute to control of M. tuberculosis.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Smita
authors.initials: S
authors.lastname: Srivastava
authors.forename: Joel D
authors.initials: JD
authors.lastname: Ernst
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma